Rifampicin Mono-Resistant Tuberculosis—A Review of an Uncommon But Growing Challenge for Global Tuberculosis Control

Malenfant, Jason H; Brewer, Timothy F.

doi:10.1093/ofid/ofab018

Cited by 25 publications

(19 citation statements)

References 59 publications

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“…The low proportions of INH mono-resistance at 9.8% (4.8–17.3) in this study may be attributed to a selection bias as a result of our selected study population. However, the higher proportions of RIF mono-resistance at 90.2% (82.7–95.2) are in agreement with two studies that raise awareness of increasing levels of this type of drug resistance among TB patients [ 24 , 25 ]. Malenfant and Brewer [ 24 ] recently reported that the availability of diagnostic assays that allow for quick detection of RIF resistance has increased awareness of patients with rifampicin mono-resistant TB (RR-TB), which was previously thought to be uncommon [ 24 ].…”

Section: Discussionsupporting

confidence: 89%

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Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

et al. 2022

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Background Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019. Methods This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients’ resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ). Results Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24–43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0–55.9) and gyrA A90V 41.1% (28.6–54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4–91.0) had A1401G mutation in the rrs gene locus. Conclusions Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings.

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Section: Discussionsupporting

confidence: 89%

“…Mono-resistance to RIF was higher than INH monoresistance and is backed by recent studies that have raised more awareness on this phenomenon [ 24 , 25 ]. The low proportions of INH mono-resistance at 9.8% (4.8–17.3) in this study may be attributed to a selection bias as a result of our selected study population.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

et al. 2022

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“…These longer regimens likely expose patients with mono-resistance to unnecessarily long and toxic drug regimens, and also exclude the benefits of INH therapy [61]. BEAT TB is at the enrolment stage assessing the efficacy of 6 months of BDQ, LZD, delamanid (DLM), LFX and CFZ in comparison to current practices in South Africa [62].…”

Section: Phase I Phase Ii Phase Iii Approvalmentioning

confidence: 99%

New developments in tuberculosis diagnosis and treatment

Gill

Dolan

Piggott

et al. 2022

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Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. It is estimated that 25% of the world's population are infected with Mycobacterium tuberculosis, with a 5–10% lifetime risk of progression into TB disease. Early recognition of TB disease and prompt detection of drug resistance are essential to halting its global burden. Culture, direct microscopy, biomolecular tests and whole genome sequencing are approved methods of diagnosis; however, their widespread use is often curtailed owing to costs, local resources, time constraints and operator efficiency. Methods of optimising these diagnostics, in addition to developing novel techniques, are under review. The selection of an appropriate drug regimen is dependent on the susceptibility pattern of the isolate detected. At present, there are 16 new drugs under evaluation for TB treatment in phase I or II clinical trials, with an additional 22 drugs in preclinical stages. Alongside the development of these new drugs, most of which are oral medications, new shorter regimes are under evaluation. The aim of these shorter regimens is to encourage patient adherence, and prevent relapse or the evolution of further drug resistance. Screening for TB infection, especially in vulnerable populations, provides an opportunity for intervention prior to progression towards infectious TB disease. New regimens are currently under evaluation to assess the efficacy of shorter durations of treatment in this population. In addition, there is extensive research into the use of post-exposure vaccinations in this cohort. Worldwide collaboration and sharing of expertise are essential to our ultimate aim of global eradication of TB disease.Educational aimsDifferentiate between TB infection and TB disease.Understand the different methods of diagnosing TB disease and resistance.Recognise the different drugs and regimens currently in use for TB disease.Be able to discuss risk of TB disease in TB infection, and assist patients in making an informed decision on treatment for TB infection.

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“…On the other hand, approximately a half-million new cases of rifampicin-resistant TB (RR-TB) were detected in 2018; according to the WHO, MDR-TB requires longer treatments, which are less effective and much more expensive than non-resistant TB [ 143 ].…”

Section: Global Problem Of Antibiotic Resistancementioning

confidence: 99%

Impact of Antibiotics as Waste, Physical, Chemical, and Enzymatical Degradation: Use of Laccases

et al. 2022

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The first traces of Tetracycline (TE) were detected in human skeletons from Sudan and Egypt, finding that it may be related to the diet of the time, the use of some dyes, and the use of soils loaded with microorganisms, such as Streptomyces spp., among other microorganisms capable of producing antibiotics. However, most people only recognise authors dating between 1904 and 1940, such as Ehrlich, Domagk, and Fleming. Antibiotics are the therapeutic option for countless infections treatment; unfortunately, they are the second most common group of drugs in wastewaters worldwide due to failures in industrial waste treatments (pharmaceutics, hospitals, senior residences) and their irrational use in humans and animals. The main antibiotics problem lies in delivered and non-prescribed human use, use in livestock as growth promoters, and crop cultivation as biocides (regulated activities that have not complied in some places). This practice has led to the toxicity of the environment as antibiotics generate eutrophication, water pollution, nutrient imbalance, and press antibiotic resistance. In addition, the removal of antibiotics is not a required process in global wastewater treatment standards. This review aims to raise awareness of the negative impact of antibiotics as residues and physical, chemical, and biological treatments for their degradation. We discuss the high cost of physical and chemical treatments, the risk of using chemicals that worsen the situation, and the fact that each antibiotic class can be transformed differently with each of these treatments and generate new compounds that could be more toxic than the original ones; also, we discuss the use of enzymes for antibiotic degradation, with emphasis on laccases.

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Rifampicin Mono-Resistant Tuberculosis—A Review of an Uncommon But Growing Challenge for Global Tuberculosis Control

Cited by 25 publications

References 59 publications

Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

New developments in tuberculosis diagnosis and treatment

Impact of Antibiotics as Waste, Physical, Chemical, and Enzymatical Degradation: Use of Laccases

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